Higher vertebrate animals such as human beings have two types of immune mechanisms (immune system), i.e., an innate immunity and an acquired immunity, and are protected from infection by allowing both the immune mechanisms to act appropriately. Meanwhile, many remaining organisms such as insects do not have the acquired immune mechanism, and are protected from the infection by the innate immune mechanism alone.
The innate immune mechanism is a defense mechanism against infection that the organisms have in common, and is characterized by its rapid reactions and effectively working against many infectious sources because this mechanism is non-specific. In the higher vertebrate animals including the human beings, it is believed that the non-specific innate immunity is more important in terms of resistance in early infection, prevention of cancers and lifestyle related diseases and tissue repair than the acquired immunity specific for the infectious source.
The infections with many infectious sources activate antigen-presenting cells such as macrophages and dendritic cells, and induce the production of cytokines such as IL-1, IL-6, IL-12 and TNF-α in the innate immune mechanism. These cytokines act upon NK cells to induce the production of IFN-γ. This produced IFN-γ acts upon the macrophages to amplify the production of IL-12 and additionally also induces the production of NO. NO rapidly reacts with oxygen and superoxide, and various chemicals produced during its process destroy the infectious source.
The abnormality in the innate immune mechanism causes various diseases. Therefore, development of excellent innate immunity activators and innate immunity suppressors capable of desirably regulating such an innate immune mechanism has been desired. Conventionally, when a substance that can be an active ingredient of such innate immunity activators and innate immunity suppressors is searched, a method in which a material to be tested is added to cultured immunocompetent cells such as macrophages from a mammalian animal and release of the cytokine such as IL-6 and TNF-α is detected by ELISA has been employed.
However, in such a conventional method, equipments for culturing the cells are required, and there has been a problem that a substance that has problems for pharamaco-kinetics in an individual when administered to the individual is also detected. Also, lipopolysaccharide (LPS) derived from bacteria and contaminated in the material to be tested reacts at low concentration, thus many materials to be tested exhibit false positive, and this has been an obstacle in the search of a novel substance.
In recent years, the method of screening the substance that acts upon the innate immune mechanism utilizing transgenic Drosophila has been proposed (e.g., see Patent Document 1), but a body length is very short, and thus it is difficult to inject a certain amount of a test liquid into a body fluid or an intestine, which is possible in silkworm larvae. It is also difficult to isolate an organ to subject to a pharmacological experiment, which is also possible in the silkworm larvae. Further, in this method, there is also a problem that only a mechanism to which a particular antibacterial peptide is related can be detected because a reporter gene is introduced downstream of an antibacterial peptide gene.
Patent Document 1: JP 2004-121155-A